G protein-coupled receptors (GPCRs) constitute a family of proteins sharing a common structural organization characterized by an extracellular N-terminal end, seven hydrophobic alpha helices putatively constituting transmembrane domains and an intracellular C-terminal domain. GPCRs bind a wide variety of ligands that trigger intracellular signals through the activation of transducing G proteins (Caron, et al., Rec. Prog. Horm. Res. 48:277–290 (1993); Freedman et al., Rec. Prog. Horm. Res. 51:319–353 (1996)).
More than 300 GPCRs have been cloned thus far and it is generally assumed that there exist well over 1000 such receptors. Mechanistically, approximately 50–60% of all clinically relevant drugs act by modulating the functions of various GPCRs (Cudernann, et al., J. Mol. Med. 73:51–63 (1995)). Of particular interest are receptors located in the central nervous system. G protein-coupled receptors located in this region are known to be involved in the transmission, modulation and sensation of pain. Thus, new G protein-coupled receptors found in the brain and spinal column may be used in assays for the identification of new agents for producing anesthesia and analgesia.